Imaging system for intra-operative and post-operative blood perfusion monitoring

ABSTRACT

Embodiments described herein generally relate to devices, methods and systems for determining blood oxygenation. By applying near infrared radiation of an appropriate wavelength to the tissue and determining the absorbance at a plurality of points where the distance between the source of the near infrared radiation and the detector are known, the oxygenation state of the hemoglobin can be determined based on position in a three dimensional space.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 14/537,509 filed Nov. 10, 2014, which is a non-provisionalapplication of U.S. provisional patent application Ser. No. 61/902,054,filed Nov. 8, 2013, which is herein incorporated by reference.

BACKGROUND Field

Embodiments disclosed herein generally relate to devices, methods andsystems for measuring tissue perfusion.

Description of the Related Art

Reconstructive surgeries, such as flap surgery, consist of thetransplantation of healthy tissue, such as a skin graft or flap, from adonor site to a wounded recipient area affected by loss of tissue. Theloss of tissue may be related to a specific trauma, such as trauma dueto burn, laceration or cancer removal. The transplanted tissue usuallycomprises skin, underlying adipose tissue, or muscle, but it can alsoconsist of composite tissues (skin and fat, skin and fat and muscle,etc.) or other organs. When possible, the tissue is transplanted from anearby area without disconnecting the vascular network. However, incertain cases, the tissue must be transplanted from a different area ofthe body (also referred to as a free flap), and the vascular network isreconnected to the existing blood vessels of the recipient area.

After detachment from the donor site, whether transplanted from a nearbyarea or different area of the body, it is crucial to re-establish bloodperfusion throughout the transplanted tissue in a timely manner and withhigh accuracy to guarantee a successful long-term outcome. If the tissueis not properly perfused in a timely fashion, the tissue will diethrough a process known as necrosis. A number of techniques have beendeveloped to determine whether the tissue has been properly perfused,with varying levels of success.

During the reconstructive procedure, surgeons can use a Dopplerultrasound pencil probe to assess if blood flow is re-established in thevessels underneath the transplanted skin. Although of some value, thismethod only allows coarse assessment of blood flow in major vessels byproducing audible feedback which is indicative of blood flow to thesurgeon. Specifically, ultrasound techniques can grossly show that bloodflow is being received by the area, but they do not provide informationregarding the direction of blood flow or the oxygenation of the bloodreceived by the transplanted tissue. Doppler ultrasound is sensitive toblood flow, primarily in arteries and arterioles. Doppler ultrasoundrelies on the technique and the interpretation of the surgeon of thewhooshing sound produced by the Doppler device in response to detectedblood flow, which is highly subjective and sensitive to technique.Oftentimes this leads to a binary interpretation (“flow/no flow”) thatdoes not represent the accurate status of tissue oxygenation, and mightlead to inaccurate clinical decisions. Moreover, the technique gives nomeasure of perfusion at the periphery of the transplanted tissue, as itis supplied by much smaller capillaries which are not detectable by useof the Doppler device.

Contrast medium imaging using fluorescent dye is an effectivemethodology to infer information about circulation in large andmedium-sized vessels, but it does not provide reliable information onmicrocirculation in the transplanted tissue. In addition, it isinherently qualitative and its applicability is limited to the operatingroom where internal tissues are exposed to direct illumination of theimaging system.

Laser Doppler Flowmetry (LDF) is another technique which has been usedto determine blood perfusion. In LDF, a beam of laser light is deliveredto a volume of tissue. Blood cells in the volume of tissue which arestruck by laser light will partly reflect it, whereupon the lightundergoes a Doppler shift. The light in the volume of tissue will be amixture of unshifted and Doppler-shifted components, the magnitude andfrequency distribution of the latter being related to the number andvelocity of moving blood cells within the volume of tissue. Similar tocontrast medium imaging, LDF can provide imaging of blood perfusion onlyin superficial skin layers, i.e., tenths of microns below the skinsurface.

Near Infrared Spectroscopy (NIRS) has been shown to be useful in plasticsurgery and transcranial oxygenation detection. NIRS uses near infrared(NIR) radiation to penetrate the underlying tissue where specificfrequencies will be absorbed or back-scattered primarily based on theoxygenation state of hemoglobin. However, current NIRS devices andmethods determine oxygenation at a single point or region withoutmapping or providing oxygenation data based on depth at multiple pointsin real time.

Thus, there is a need in the art for better visualization of the bloodflow and the oxygenation state of the blood, and to track changes overtime (including after a patient has been discharged home followingsurgery).

SUMMARY

The embodiments described herein generally relate to methods, devicesand systems for visualization of blood flow and oxygenation.

In one embodiment, an imaging device can include a support comprising afirst surface; a plurality of first radiation sources positioned at afirst interval on the first surface, each of the plurality of firstradiation sources delivering radiation at a first interval and a firstwavelength range, the first wavelength range comprising one or morefirst wavelengths between about 650 nm and about 1000 nm; a plurality ofsecond radiation sources positioned at the first surface, the secondradiation sources delivering radiation at a second interval and a secondwavelength range, the second wavelength range comprising one or moresecond wavelengths between about 650 nm and about 1000 nm, at least oneof the one or more second wavelengths being different than at least oneof the one or more first wavelengths, wherein each of the plurality ofsecond radiation sources is positioned adjacent one of the plurality offirst radiation sources creating a plurality of associated radiationsources; and a detector positioned at the first surface, the detectorpositioned a first distance from each of the first radiation sources andeach of the second radiation sources, and the detector detectingradiation at wavelengths between 650 nm and 1000 nm.

In another embodiment, a method for tissue imaging transplanted tissuecan include positioning a first radiation source and a second radiationsource in proximity to a tissue; delivering a first radiation of a firstwavelength range from the first radiation source to the tissue, thefirst wavelength range being between about 650 nm and about 1000 nm, thetissue absorbing a portion of the first radiation creating a firsttransmitted radiation; detecting the first transmitted radiation at adetector positioned a first distance from the first radiation source,wherein the path traveled by the first transmitted radiation through thetissue creates a first mean radiation path; delivering a secondradiation of a second wavelength range from the second radiation sourceto the tissue, the second wavelength range being between about 650 nmand about 1000 nm, wherein the tissue absorbs a portion of the secondradiation creating a second transmitted radiation; detecting the secondtransmitted radiation at a detector positioned a second distance fromthe second radiation source, wherein the path traveled by the secondtransmitted radiation through the tissue creates a second mean radiationpath; determining an overlap absorbance between the first mean radiationpath and the second mean radiation path; repeating the steps of deliveryof the first radiation, the detection of the first transmittedradiation, the delivery of the second radiation, the detection of thesecond transmitted radiation and the determining of the overlapabsorbance using a plurality of first radiation sources and a pluralityof second radiation sources to create a plurality of overlapabsorbances; and mapping the plurality of overlap absorbances on acoordinate plane, wherein the mapped absorbances create a map ofoxygenated and deoxygenated regions of hemoglobin in the tissue overtime.

In another embodiment, a system for tissue imaging can include a supportcomprising a first surface and configured to support a plurality ofdevices in proximity to a tissue, the tissue comprising both oxygenatedand deoxygenated hemoglobin; a plurality of radiation sources positionedon the first surface, the radiation sources configured to deliver afirst radiation of a first wavelength range to the tissue, the firstwavelength range including wavelengths between about 650 nm and about1000 nm, wherein the tissue absorbs at least a portion of the firstradiation; and deliver a second radiation of a second wavelength rangeto the tissue, the second wavelength range including wavelengths betweenabout 650 nm and about 1000 nm, the second wavelength range partiallyoverlapping the first wavelength range, wherein the tissue absorbs atleast a portion of the second radiation; a plurality of detectorspositioned at a first interval on the first surface of the support, theplurality of detectors configured to detect a back-scattered portion ofthe first radiation and a back-scattered portion of the secondradiation; and provide a signal regarding each of the wavelengthsdetected; and a control device configured to control the radiationsources such that the first radiation and the second radiation isdelivered in a multiplexed fashion; determine an amount of absorption bythe tissue from each of the first radiation and the second radiationusing the intensity of the back-scattered portion of the first radiationand the intensity of the back-scattered portion of the second radiation;determine a location of absorption in the tissue using the position ofthe first radiation source and the second radiation source in relationto the detector; and create a map of oxygenated and deoxygenatedhemoglobin in the tissue using the amount of absorption and the locationof absorption.

In another embodiment, an imaging device can include a near infraredspectroscopy (NIRS) device having a support comprising a first surface;a plurality of radiation sources positioned in connection with the firstsurface; a plurality of radiation detectors positioned in connectionwith the first surface; a processor in connection with the near infraredspectroscopy device; and a non-transitory memory adapted to store aplurality of machine-readable instructions. The plurality ofmachine-readable instructions can, when executed by the processor, causethe imaging device to create a volumetric map, the dimensions of thevolumetric map corresponding to the tissue portion; subdivide thevolumetric map into volumetric subregions, the volumetric subregionscomprising a plurality of voxels, each voxel being assigned eitherpreassigned values or random values; overlay a sensitivity map onto thevolumetric map, the sensitivity map having a photon migration pattern;perform at least one iterative cycle; and repeat the iterative cycleuntil either a preset maximum is reached or the measurement error isless than a present threshold.

The iterative cycle can include determining the measurement array andthe calculated array for the volumetric map, the measurement arraycomprising optical measurements corresponding to the photon migrationpattern, the calculated array comprising determined measurementscorresponding to the assigned value as weighted by the photon migrationpattern; increasing an assigned value of a test voxel of the volumetricmap, each of the test voxel being selected from the voxels of thevolumetric subregions, the increase perturbing the volumetric map;calculating perturbed determined measurements of a perturbed calculatedarray for the volumetric map; and determining an error between themeasurement array and the perturbed calculated array of the volumetricmap, wherein if the perturbation causes the error to go down, then avolumetric Gaussian kernel having a radius is centered on the test voxeland extending to a plurality of proximate voxels, the test voxel and theproximate voxels being permanently increased in perfusion proportionallyto the magnitude of the error decrease multiplied by a proportionalfactor A, and wherein if the perturbation causes the error to go up,then a volumetric Gaussian kernel having a radius is centered on thetest voxel and extending to a plurality of proximate voxels, the testvoxel and the proximate voxels being permanently decreased in perfusionproportionally to the magnitude of the error increase multiplied by aproportional factor A.

In another embodiment, a method for tissue imaging in a transplantedtissue can include positioning a near infrared spectroscopy (NIRS)device in connection with a tissue portion located on a donor locationof a first body, the NIRS device being positioned for a near infraredmeasurement; collecting a first NIRS measurement using the NIRS device,the first NIRS measurement providing volumetric information regardingblood oxygenation or tissue perfusion; removing the tissue portion fromthe donor location of the first body; transplanting the tissue portionto a recipient location of the first body or a second body; collecting asecond NIRS measurement, the second NIRS measurement providingvolumetric information regarding blood oxygenation or tissue perfusion;and comparing the first NIRS measurement to the second NIRS measurementto determine a change in blood oxygenation or tissue perfusion.

In another embodiment, a system for tissue imaging can include a nearinfrared spectroscopy (NIRS) device having a support comprising a firstsurface and configured to support a plurality of devices in proximity toa tissue, the tissue comprising both oxygenated and deoxygenatedhemoglobin; a plurality of radiation sources positioned on the firstsurface; and a plurality of radiation detectors positioned in connectionwith the first surface; and a control device having a processor inconnection with the NIRS device; and a non-transitory memory adapted tostore a plurality of machine-readable instructions.

The radiation sources can be configured to deliver a first radiation ofa first wavelength range to the tissue, wherein the tissue absorbs atleast a portion of the first radiation; and deliver a second radiationof a second wavelength range to the tissue, the second wavelength rangepartially overlapping the first wavelength range, wherein the tissueabsorbs at least a portion of the second radiation. The plurality ofdetectors can be configured to detect a back-scattered portion of thefirst radiation and a back-scattered portion of the second radiation;and provide a signal regarding each of the wavelengths detected.

The plurality of machine-readable instructions can, when executed by theprocessor, cause the near infrared spectroscopy device to create avolumetric map, the dimensions of the volumetric map corresponding tothe tissue portion; subdivide the volumetric map into volumetricsubregions, the volumetric subregions comprising a plurality of voxels,each voxel being assigned either preassigned values or random values;overlay a sensitivity map onto the volumetric map, the sensitivity maphaving a photon migration pattern; perform at least one iterative cycle;and repeat the iterative cycle until either a preset maximum is reachedor the measurement error is less than a present threshold.

The iterative cycle can include determining the measurement array andthe calculated array for the volumetric map, the measurement arraycomprising optical measurements corresponding to the photon migrationpattern, the calculated array comprising determined measurementscorresponding to the assigned value as weighted by the photon migrationpattern; increasing an assigned value of a test voxel of the volumetricmap, each of the test voxel being selected from the voxels of thevolumetric subregions, the increase perturbing the volumetric map;calculating perturbed determined measurements of a perturbed calculatedarray for the volumetric map; and determining an error between themeasurement array and the perturbed calculated array of the volumetricmap, wherein if the perturbation causes the error to go down, then avolumetric Gaussian kernel having a radius is centered on the test voxeland extending to a plurality of proximate voxels, the test voxel and theproximate voxels being permanently increased in perfusion proportionallyto the magnitude of the error decrease multiplied by a proportionalfactor A, and wherein if the perturbation causes the error to go up,then a volumetric Gaussian kernel having a radius is centered on thetest voxel and extending to a plurality of proximate voxels, the testvoxel and the proximate voxels being permanently decreased in perfusionproportionally to the magnitude of the error increase multiplied by aproportional factor A.

BRIEF DESCRIPTION OF THE DRAWINGS

So that the manner in which the above recited features of the presentinventions can be understood in detail, a more particular description ofthe inventions, briefly summarized above, may be had by reference toembodiments, some of which are illustrated in the appended drawings. Itis to be noted, however, that the appended drawings illustrate onlytypical embodiments of this inventions and are therefore not to beconsidered limiting of its scope, for the inventions may admit to otherequally effective embodiments.

FIG. 1A depicts a top view of a device according to an embodimentdisclosed herein;

FIG. 1B depicts the device with the plurality of interdistancesaccording to one embodiment disclosed herein.

FIG. 1C depicts a side view of the device positioned in connection witha tissue according to an embodiment disclosed herein;

FIG. 1D depicts the device in connection with a data collection unit,according to one embodiment disclosed herein;

FIG. 2 is a block diagram of machine-readable instructions forprocessing near infrared spectroscopy information, according to oneembodiment;

FIGS. 3A-3C depict a system according to an embodiment disclosed herein;

FIG. 4 depicts an example of a slice of the absorbance detected using anNIRS device, according to an embodiment disclosed herein;

FIG. 5 depicts a map of the absorbance detected using a device,according to an embodiment disclosed herein;

FIGS. 6A and 6B are a flow diagram of a method of mapping perfusionaccording to an embodiment; and

FIG. 7 is a block diagram of a method of transplanting a tissue,according to one embodiment.

To facilitate understanding, identical reference numerals have beenused, where possible, to designate identical elements that are common tothe figures. It is contemplated that elements and features of oneembodiment may be beneficially incorporated in other embodiments withoutfurther recitation.

DETAILED DESCRIPTION

Embodiments disclosed herein generally relate to methods devices andsystems for visualization of blood flow and oxygenation in any livingtissue. The device described here uses near infrared (NIR) radiation ata plurality of points through a probe in contact with the skin toproduce a three dimensional map of blood flow and oxygenation. A map ofthe blood flow and oxygenation is created using the detected absorptionof the NIR radiation. The methods, devices and systems described hereincan detect both the existence and location of arterial occlusions,venous occlusions and other alterations of normal perfusion during asurgical procedure and in a non-invasive fashions. Further, the imagesforming the map can be produced at real-time intervals, such as everysecond or less.

In addition to the above scope of utility, this imaging system has wideutility in the assessment of tissue viability in many other scenarios,such as compartment syndrome (after a leg crush injury, for example) andeven intraoperative assessment of organ tissue viability during certainsurgical procedures.

The NIRS device can be placed in contact with the skin of the subject.The NIRS device delivers the NIR radiation several centimeters beneaththe skin. A portion of the NIR radiation is then back-scattered backtoward the surface where it is detected by a plurality of radiationdetectors, such as photodetectors. This back-scattered radiationprovides information about the absorbance within a specific area of thetissue and can be used to produce a color coded map of the perfusion ofthe targeted tissue. The color coded volumetric map, which can be aperfusion map or an oxygenation map, is generated using theback-scattered radiation as an indication of the absorbed wavelengths ineach portion of the tissue. The wavelengths are absorbed differently byoxygenated and deoxygenated hemoglobin. The absorption intensity andlocation provide a pattern based on the oxygenation state of thehemoglobin, which can be incorporated into a three dimensional (3D) mapto visualize the oxygenation and deoxygenation of hemoglobin in thetissue. The embodiments disclosed herein are more clearly described withreference to the figures below.

FIG. 1A depicts a top view of a NIRS device 100 according to anembodiment. The NIRS device 100 includes a support 102 which supports aplurality of additional components of the NIRS device 100. The support102 can be made of a material used in electronic devices, such assilicon, germanium or other suitable materials. In one embodiment, thesupport 102 is a standard circuit board. The support 102 may be flexibleor rigid. The support 102 may be of a shape and size to accommodate thearea being probed and the needs of the user or the subject. The support102 shown here is an octagonal shape. However, the support 102 can be acircle, a square, a triangle, combinations thereof or permutationsthereof. The support has a first surface 103 and a second surface (notshown) opposite the first surface. The first surface 103, thoughdepicted as flat, may be flat, curved, wavy or other shapes as needed ordesired by the user or the subject.

The support 102 can have a plurality of radiation sources 104 a-104 ff.The radiation sources 104 a-104 ff can be any available source ofradiation, such as a light emitting diode (LED), a laser source or otherradiation sources. Further, the radiation sources 104 a-104 ff can belight delivery devices in connection with a radiation source, such as afiberoptic wire in connection with a radiation source listed above. Theradiation sources 104 a-104 ff can be discrete components which arepositioned on the support 102 or the radiation sources 104 a-104 ff canbe integrated into the support 102. In this embodiment, the radiationsources 104 a-104 ff are integrated into the support 102. The radiationsources 104 a-104 ff can be positioned anywhere on the surface of thesupport. Here, the radiation sources 104 a-104 p form a first circlewith a center at the center of the support 102 and radiation sources 104q-104 ff form a second circle which is concentric with the first circle.

The plurality of radiation sources 104 a-104 ff can be separated into aset, shown here as sixteen (16) groups of two. For example, radiationsource 104 b and radiation source 104 c are part of a set. However,larger sets of the plurality of radiation sources 104 a-104 ff arepossible. For clarity of discussion, the radiation sources 104 b, 104 d,104 f, 104 h, 104 j, 104 l, 104 n, 104 p, 104 r, 104 t, 104 v, 104 x,104 z, 104 bb, 104 dd and 104 ff can also be referred to as the firstradiation sources of the set and the radiation sources 104 a, 104 c, 104e, 104 g, 104 i, 104 k, 104 m, 104 o, 104 q, 104 s, 104 u, 104 w, 104 y,104 aa, 104 cc and 104 ee can also be referred to as the secondradiation sources of the set. The first radiation sources of each setcan be positioned in close proximity or adjacent to the second radiationsources of the set. Further, the first radiation sources and the secondradiation sources of each set can be equidistant from one or more of thedetectors 106 a-106 e. For example, the radiation source 104 d and theradiation source 104 e are equidistant from the detector 106 a. Thispositioning will allow two separate wavelengths or ranges of wavelengthsto be delivered over largely the same area such that the absorptionpatterns can be determined and mapped.

The radiation sources 104 a-104 ff can produce radiation at wavelengthsfrom about 650 nm to about 1000 nm. At least one radiation source ofeach of the sets of radiation sources produces a range of radiationwavelengths. The range of radiation wavelengths has at least a portionof the wavelengths between about 650 and about 1000 nm, such as betweenabout 800 nm and about 950 nm. In one embodiment, at least one of theradiation sources of the set of radiation sources produces a range ofradiation wavelengths including a wavelength of 880 nm. Shown here, theradiation sources 104 b, 104 d, 104 f, 104 h, 104 j, 104 l, 104 n, 104p, 104 r, 104 t, 104 v, 104 x, 104 z, 104 bb, 104 dd and 104 ff (thefirst radiation sources of the set) produce radiation between about 650nm and about 1000 nm. Further, at least one of the plurality ofradiation sources 104 produces a range of radiation wavelengths. Therange of radiation wavelengths has at least a portion of the wavelengthsbetween about 650 and about 1000 nm, such as between about 650 and about800 nm. In one embodiment, at least one of the radiation sources of theset of radiation sources produces a range of radiation wavelengthsincluding a wavelength of about 660 nm. The radiation sources 104 a, 104c, 104 e, 104 g, 104 i, 104 k, 104 m, 104 o, 104 q, 104 s, 104 u, 104 w,104 y, 104 aa, 104 cc and 104 ee (the second radiation sources of theset) produce radiation from about 650 and about 1000 nm. In thisembodiment, the first radiation sources of each set produce at least onewavelength which is not produced by the second radiation sources of therespective set. In one example, the radiation source 104 b produces atleast one radiation wavelength which is different from the radiationsource 104 c.

The support 102 can further include one or more detectors 106 a-106 e.The detectors 106 a-106 e can be any device which detects one or morewavelengths of radiation. The detectors 106 a-106 e may bephotodetectors, such as a photoconductor, a junction photodetector,avalanche photodiodes, other types of detectors which can directlydetect radiation, indirectly detect radiation or combinations thereof.The detectors 106 a-106 e can be discrete components which arepositioned on the support 102 or the detectors 106 a-106 e can beintegrated into the support 102.

FIG. 1B depicts the NIRS device 100 with the plurality of interdistancesaccording to one embodiment disclosed herein. The interdistance in thespace between one of the plurality of radiation sources 104 a-104 ff andone of the plurality of detectors 106 a-106 e. As the radiationdelivered from each of the radiation sources 104 a-104 ff will diffusein the tissue in all directions, each of the detectors 106 a-106 e willreceive some radiation from each of the radiation sources 104 a-104 ff.Therefore, the positioning of the plurality of detectors 106 a-106 e andthe plurality of radiation sources 104 a-104 ff creates a web ofinterdistances, exemplified here as interdistances 108 a-108 f. Tomaintain clarity, not all interdistances are shown in FIG. 1B.

In FIG. 1C, the NIRS device 100 can be positioned in proximity to atissue 120. The tissue 120 can be a human tissue, such as that which istransplanted or grafted during reconstructive surgery. In this sideview, only detector 106 a and radiation sources 104 e, 104 u, 104 bb,and 104 l are visible, The detector 106 a and radiation sources 104 e,104 u, 104 bb, and 104 l are positioned on the support 102 with aspecific interdistance between them. It is believed that the maindeterminant of the detection depth 116, when composition of the tissue120 is not considered, is the interdistances between the radiationsource and the detector, such as the interdistance between the radiationsources 104 e, 104 u, 104 bb, and 104 l and the detector 106 a.Radiation that happens to travel close to the surface of the tissue 120is very likely to be lost out of the tissue 120 before reaching thedetector. Thus, interdistance between the radiation source and thedetector will not detect most of the radiation which travels close tothe surface except in the portion of the tissue 120 directly under theradiation sources 104 e, 104 u, 104 bb, and 104 l and the detector 106a. On the other hand, radiation which is not sufficiently scattered,radiation which is scattered in other directions or radiation which isabsorbed by the tissue 120 is not returned to the detector 106 a. Theremaining radiation, excluding the lost radiation between the radiationsource 104 and the detector 106 and the distant radiation which does notreturn to the detector 106, create a mean radiation path 114 in anarcuate shape shown in FIG. 1C. By modulating the interdistance betweenthe radiation source 104 and the detector 106, the average detectiondepth 116 can also be modulated.

Radiation between about 650 nm and about 1000 nm can be used to identifythe position and quantity of hemoglobin in the tissue 120. Hemoglobinhas a wide absorbance range, for both the HHb and HbO₂ states, in therange of about 650 nm to about 1000 nm. The isosbestic point between HHband HbO₂ is about 808 nm. The isosbestic point is a specific wavelengthat which two chemical species have the same molar absorptivity. Thus,HHb is the primary absorbing component in the range of between about 650nm to about 808 nm and HbO₂ is the primary absorbing component in therange of between about 808 nm and about 1000 nm. At wavelengths below650 nm, the absorption of hemoglobin is too high which would preventanything but superficial measurement of the specific subtype. Atwavelengths above 1000 nm, the absorption of water is too high whichwould prevent measurement of absorption of either HHb or HbO₂. Using theabsorbance ranges described above, the overall quantity of hemoglobin inan area can be determined while differentiating between HHb and HbO₂ inthe same area.

As described above, the interdistance between one of the radiationsources 104 and one of the detectors 106 can be used to increase ordecrease the detection depth 116 a-116 d. It is further believed thatthe detection depth 116 a-116 d at the midpoint between one of thedetectors 106 and one of the radiation sources 104 is approximately ⅔ ofthe interdistance between the detector 106 and the radiation source 104.The positioning of the radiation sources 104 and the detectors 106creates a plurality of mean radiation paths 114. The mean radiationpaths 114 are the average path for radiation through the tissue 120,which penetrates to various depths and overlaps with other meanradiation paths 114. The information provided by the mean radiationpaths 114 and their overlap can be used to create the three dimensionalmap of the HHb and the HbO₂ as well as to differentiate between thecomparative concentrations thereof, described more clearly withreference to FIGS. 3A and 3B.

A plurality of vacuum ports 112, shown in FIG. 1A, can be formed in thesupport 102. The vacuum ports 112 can be connected with a vacuum supply(not shown). The vacuum ports 112 may be of various sizes and shapes,such as the eight circular vacuum ports 112 shown here. The vacuum ports112 may be formed at the edges of the support 102 or at an internalportion of the surface 103. The vacuum ports 112 may be used to apply avacuum to an underlying surface, such as the surface of the tissue 120,thus creating a more secure connection between the surface 103 and thetissue 120. In further embodiments, the vacuum ports 112 are omitted andthe NIRS device is secured to the tissue 120 using other means, such asthrough the use of adhesives or bandages.

The distance between the NIRS device 100 and the tissue 120 should beminimized to minimize reflection of the radiation from the surface ofthe tissue 120. A media interface, such as that which forms at thesurface of the tissue 120 in the presence of atmospheric gases, cancreate a partially reflective surface to the NIR radiation. Reflectionfrom an interface surface is a function of the distance from thesurface, as radiation diffuses over a distance in atmosphere. Thus, thesurface of the tissue 120 reflects a higher proportion of thewavelengths of NIR radiation when the tissue 120 is spaced a greaterdistance from the radiation sources 104 a-104 ff. By decreasing thedistance between the radiation sources 104 a-104 ff and the tissue 120,either with or without the vacuum ports 112, the effect of reflection atthe interface is diminished.

Though, the NIRS device 100 and the related methods and technologicaladvances are depicted in the context of a specific tissue, such as theskin, the scope of the embodiments disclosed herein are not limited toany specific tissue. The scope of the methods or devices disclosedherein can easily be modified to accommodate other forms of organsurgery and in vivo applications. In one embodiment, the NIRS device 100as described herein, can provide real-time, 3-D volumetric mappingtechnology intraoperatively to image hearts coming off of bypass. Thus,the NIRS device 100 allows a clinician to assess the adequacy ofcoronary sufficiency. In another embodiment, the NIRS device 100 can beused to image renal tissue during partial nephrectomy withintraoperative vascular occlusion. In another embodiment, the NIRSdevice 100 can be applied to various types of hepatic and neurosurgicalprocedures. Additionally, given that the imaging system has the abilityto penetrate through a few centimeters of tissue, non-operative(external to the body/non-invasive) muscle mapping during exercise (oras a response to exercise) can be envisioned to aid in athleticperformance and rehabilitation medicine. Oxidative information providedby the NIRS device 100 can be applied following a stroke or other typesof physical compromise.

Additionally, the NIRS device 100 may be incorporated into otherdevices, such that a first device incorporates the functionality of theNIRS device 100 as described herein. In one embodiment, the NIRS device100 is incorporated into surgically implanted devices, such as automaticdefibrillators, pacemakers, stimulators and the like, totranscutaneously transmit organ tissue perfusion on a periodic basis.One or more wireless communication methods or protocols can then beincorporated to receive the information transmitted by the NIRS device100. For example, the oxygenation information could be sent viabluetooth or other method to a computing device, such as smartphone, atablet or a laptop. The computing device can then relay the informationto a third party, such as the patient, the patient's provider or anotherclinician.

FIG. 1D depicts the NIRS device 100 in connection with a data collectionunit 135 and a control unit 150, according to an embodiment disclosedherein. The NIRS device 100 can be connected with the data collectionunit 135 through the connection 140. The data collection unit 135 can bea single device or a plurality of devices configured to receive andprocess the information collected by NIRS device 100. The connection 140between the data collection unit 135 and the NIRS device 100 may beeither a wired or wireless connection. The connection 140 shown here isa wired connection.

The data collection unit 135 can be in connection with further devices,such as a control unit 150. In some embodiments, the data collectionunit 135, the control unit 150, the NIRS device 100 or combinations arethe same device or device component. The combination of the NIRS device100, the data collection unit 135 and the control unit 150 may bereferred to as an imaging device. The control unit 150 can include aprocessor 155 and memory 160. The control unit 150 can be configured tocollect, process or otherwise utilize the received data at the datacollection unit 135. The control unit 150 can deliver automated oruser-input instructions to the NIRS device 100 to perform one or more ofthe functions described with reference to FIG. 1A-1C. The control unit150 can also be a smartphone, an interactive display or other devices.In another embodiment, the data collection unit 135 is a computerincluding a processor and memory with instructions which, when processedby the computer, causes the computer to perform one or more of thefunctions described herein. The data collection unit 135 is connectedwith a power supply 145, which powers the data collection unit 135, theNIRS device 100, the control unit 150 or combinations thereof. The datacollection unit 135 can also be connected with further devices through awireless transmitter. In one embodiment, the data collection unit 135provides information collected by the NIRS device 100 to a nursingstation down the hall, a doctor's office or a call center. Using thecontrol device 150, the data collection unit 135 or both, an individual(e.g., a doctor or a nurse) can track changes in tissue perfusion innear real time, and call the patient back for assessment, surgery orother intervention.

The processor can be a general use processor, as known in the art.Further, the processor can be designed for the specific functions thatare disclosed herein. The processor can be designed or configured toperform one or more operations related to the detection of a nearinfrared signal or for the determination of oxygenation in a tissue. Theoperations may be represented as instructions in a machine-readableformat that are stored on the memory. The memory can be one or morenon-transitory types of computer readable media, such as solid statememories, hard drives, and the like. The instructions may residecompletely, or at least partially, within the memory and/or within theprocessor during execution.

In further embodiments, the NIRS device 100 can be coated a coating 130.The coating 130 can be an optically clear biocompatible material, suchas silicon. The coating 130 can prevent direct contact between thetissue 120 and electronic components without compromising thefunctionality due to light reflections.

FIG. 2 is a block diagram of machine-readable instructions 200 forprocessing near infrared spectroscopy information, according to oneembodiment. The memory can be adapted to store a plurality ofmachine-readable instructions. The machine-readable instructions 200can, when executed by the processor, cause the imaging device to createa sensitivity map of a tissue portion, the sensitivity map showing aphoton migration pattern for the tissue portion; create a volumetricmap, the dimensions of the volumetric map corresponding to the tissueportion; subdivide the volumetric map into volumetric subregions, thevolumetric subregions comprising a plurality of voxels, each voxel beingassigned either preassigned values or random values; overlay the photonmigration pattern of the sensitivity map onto the volumetric map;perform at least one iterative cycle; and repeat the iterative cycleuntil either a preset maximum is reached or the measurement error isless than a present threshold.

Instructions 200 can further include creating a volumetric map, thedimensions of the volumetric map corresponding to the tissue portion, at202. The volumetric map is the same volume as the tissue portion beingexamined by the NIRS device. The volumetric map begins with noinformation incorporated. The volumetric map consists of a plurality ofvoxels. The voxels are defined regions of the volumetric maprepresenting the smallest distinguishable detection area in thevolumetric map.

Instructions 200 can further include subdividing the volumetric map intovolumetric subregions, at 204. In one embodiment, the volumetric map isfurther divided into volumetric subregions. The volumetric subregionsare defined three dimensional regions in the volumetric map. Thevolumetric subregions can be non-overlapping. Further, the volumetricsubregions can share common boundaries, such that 100 percent of thevolumetric subregions is equivalent to 100 percent of the volumetricmap. Stated another way, the volumetric subregions can be composed ofthe plurality of voxels. The volumetric subregions can be formed suchthat the boundary of the volumetric subregion does not subdivide avoxel. The number of sub-regions can be fixed or can be dynamicallychanged throughout the algorithm. In one embodiment, the volumetricsubregions are dynamically changed by the exclusion of a determinedsub-region, such that the process focuses on sub-regions which have notyet been determined. In another embodiment, the volumetric subregionsare dynamically changed by changing the position of the boundaries ofthe defined subregions, such that either the shape of the subregionschange, the position of the subregions change or the number ofsubregions change.

Instructions 200 can further include assigning each voxel with eitherpreassigned values or random values. As each voxel corresponds to aportion of the tissue, it also has a volumetric value, such as anoxygenation value, that describes or relates to the detected parameterin the corresponding portion of tissue. As it is not currently feasibleto deliver radiation to each voxel individually and detect the relatedabsorbance, information must be extrapolated from the opticalmeasurement and onto the voxels of the volumetric map. The programdescribed herein extrapolates this information by providing an assumedvolumetric value for each of the voxels, based on either a predefinednumber or a random number. Possible volumetric values include opticalabsorption measurements, corresponding readings of concentration ofhemoglobin in various states, such as oxyhemoglobin (HbO₂) anddeoxyhemoglobin (HbB), or other entries which correlate to an opticallymeasurable tissue data.

Instructions 200 can further include overlaying a sensitivity map ontothe volumetric map, the sensitivity map having a photon migrationpattern, at 206. It is beneficial to know where the photons migratewithin the tissue of interest, given the superficial location of allsources and detectors. Specifically, the photon path between each sourceand each detector of the probe can be determined and then superposed forall source-detector pairs, so to obtain a volumetric map that describesthe density of photons in all locations within the tissue. This iscalled the sensitivity map. The sensitivity map is intended as the mapthat indicates which sub-regions of tissue, and which voxels, are moresensitive to the detection of a physiological change. The sensitivity isdue to a higher density of photons travelling in those regions. Incontrast, physiological changes in regions of the tissue where there isno photon travelling will not be directly measurable by opticalabsorption (i.e., region of the sensitivity map that has a nullsensitivity). The sensitivity map relates to the geometric layout oflight sources and detectors and to the anatomical properties of thetissue being investigated.

The reconstruction of a volumetric map of blood perfusion or changesthereof can be described as an inverse problem. An inverse problem is aproblem where the effect of a physiological phenomenon is known (e.g.,by taking single or multiple measurements at any given point in time,for a single or multiple points in time) and a description of theoriginating phenomenon (e.g., the quantity of oxyhemoglobin (HbO₂) anddeoxyhemoglobin (HbB)) is sought as a result. As opposed to the “forwardproblem” (which is calculating the measurable effect of a knownoriginating phenomenon), the inverse problem is substantially moredifficult to solve, mainly because a dense representation of the source(in one example, a perfusion image consisting of thousands of voxels) isattempted starting from sparse measurements of the effect (i.e., fewdozens of optical measurements).

One approach to the solution of the inverse problem is iterativeapproach. The volumetric map is initially defined, as described above,and it is subsequently adjusted over a certain number of iterations,until the volumetric map is deemed to be sufficiently accurate. Thestrategy for adjusting the map at any step of the iterative cycle isbased on the error between the actual measurements of the effect(optical measurements or concentration measurements) and themeasurements calculated by solution of the forward problem using theestimated volumetric map. As described here, The sum of the assumedvolumetric values are then transformed using the sensitivity map.

If the error has a downward trend during subsequent map adjustments, itmeans that the applied adjustments to the map are going in the rightdirection and the volumetric map is converging towards a solution of theinverse problem. If the error has an upward trend during subsequent mapadjustments, the applied adjustments are wrong and must be corrected insubsequent iterations. The iterative process ends when the error betweenthe actual and estimated measurement is sufficiently low, indicatingthat the current estimated volumetric map is in fact originating aneffect measurement that is sufficiently close to the actual measurement.

To solve the forward problem, it is necessary to know where the photonsmigrate within the tissue of interest, given the location of all sourcesand detectors in the NIRS device. Specifically, the photon migrationpattern between each source and each detector of the probe need to bedetermined. The photon migration pattern can then be superposed for allsource-detector pairs, which creates a sensitivity map that describesthe density of photons derived from the source in all locations withinthe tissue portion.

Instructions 200 can further include performing at least one iterativecycle, at 210. The iterative cycle can include determining themeasurement array and the calculated array for the volumetric map. Themeasurement array includes an optical measurement for the areascorresponding to the photon migration pattern in the volumetric map. Thecalculated array includes a determined measurement of the equivalentmigration pattern of the volumetric subregion. The optical measurementis the optical measurement of the radiation delivered from each of theradiation sources to the tissue and received by each of the detectors,as affected by absorbance in the corresponding region of tissue (i.e.,the tissue in the photon migration pattern). The optical measurement canbe performed as described below with relation to FIGS. 2-3C. Thedetermined measurements is the calculated equivalent to the opticalmeasurement, as calculated from the voxels of the volumetric map whichcorrespond to the photon migration pattern and weighted based on thesensitivity map.

In one embodiment, the measurement is a single measurement for allradiation source/detector combinations. The single measurement can beused throughout all iterative cycles. Each of the measurement array andthe calculated array include a number of values related to the totalnumber of radiation source/detector combinations. In one embodiment,there are sixty-four (64) radiation source/detector combinations.Therefore, in this embodiment, there are sixty-four (64) actual opticalmeasurements in the measurement array and 64 determined measurements inthe calculated array.

The iterative cycle can further include increasing an assigned value ofa test voxel and calculating a perturbed calculated array for thevolumetric map, wherein the volumetric map is perturbed at a test voxelwithin the selected subregion. Using the embodiment described above, asingle assigned value is changed for a test voxel. The assigned valuecan be a perfusion value. The 64 determined measurements for thecalculated array are produced from the volumetric map. The 64 determinedmeasurements (i.e., the calculated array) are then compared to the 64actual optical measurements (i.e., the measurement array) to determinethe distance between the values.

Each of the test voxels are selected from the voxels of the volumetricsubregions. As stated above, the voxels of the volumetric map are givenan assigned value, which can be either arbitrary or predefined. When thetest voxel is increased in value, the increase will perturb the value ofthe measurement corresponding to the volumetric subregion. The perturbedcalculated array, which is the sum of the values of the voxels in thevolumetric map as transformed by the sensitivity map, can then becalculated for each of the photon migration patterns.

In one embodiment, predefined can mean defined through a previousiterative cycle. The iterative process converges faster when the valueassigned to the voxels of the volumetric map at the first iteration isclose to the real solution. As such, the algorithm can include thecreation of a pre-measurement volumetric map of the tissue. Thepre-measurement can have a longer than standard duration (e.g., 10-60seconds, considering that it starts from a null, or unknown image). Thepre-measurement voxel values can then be used to set the initial valueof the voxels for future measurements. It is believed that, because thephysiological changes occur quite slowly (in the order of tenth ofseconds or minutes), that an image calculated at a previous point intime would provide values which approximates the volumetric map at acurrent point in time. Further, any physiological traits of the tissueportion which affect an oxygenation parameter will be represented tosome extent in the pre-measurement volumetric map. As such, by using theindividually established values from a pre-measurement for the basevalue for the voxels in a later iterative cycle, the values will be bothmore quickly derived and more precise than arbitrary values orpreassigned values which are established in another fashion.

The iterative cycle can further include determining the error betweeneach of the optical measurements of the measurement array and theperturbed determined measurement of a perturbed calculated array. Theerror is determined using the Euclidean distance between the two pointsP and Q, where P is the measurement array and Q is the calculated array.The Euclidean distance between points P and Q is the distance betweenthe points in an Euclidean space of n-dimensions (n-space). Thus, thedistance between the points correlates to the error in the perturbeddetermined measurements of the perturbed calculated array. In oneexample, a total of 64 photon migration patterns creates a total of 64optical measurements for the volumetric map. The 64 optical measurementsare the P values, which are compared against the 64 perturbed determinedmeasurements (i.e., the Q values) The distance between these points isthe magnitude of the error. In Cartesian coordinates, if P=(P₁, P₂, . .. , P_(n)) and Q=(Q₁, Q₂, . . . , Q_(n)) are two points in Euclideann-space, then the distance (d) from P to Q, or from Q to P is given by:

$\begin{matrix}{{d\left( {p,q} \right)} = {d\left( {q,p} \right)}} \\{= \sqrt{\left( {q_{1} - p_{1}} \right)^{2} + \left( {q_{2} - p_{2}} \right)^{2} + \ldots + \left( {q_{n} - p_{n}} \right)^{2}}} \\{= {\sqrt{\sum\limits_{i = 1}^{n}\left( {q_{i} - p_{i}} \right)^{2}}.}}\end{matrix}$

If the perturbation causes the measurement error to go down, then avolumetric Gaussian kernel of sigma value S (similar to the radius of asphere) is centered on the perturbed voxel and is permanently increasedin perfusion proportionally to the magnitude of the error decreasemultiplied by a proportional factor A. If the perturbation causes themeasurement error to go up, then the perfusion map is updated bydecreasing the perfusion locally in a volumetric Gaussian kernel ofsigma value S and centered on the perturbed voxel and is permanentlydecreased in perfusion proportionally to the magnitude of the errorincrease multiplied by a proportional factor A. The machine-readableinstructions 200 can be executed sequentially or in a predeterminedorder.

The sigma value S is an assigned value which corresponds to the radiusof the Gaussian kernel from a starting point of the center of the testvoxel. The value S is not necessarily a static value and can changethroughout the iterations. The proportional factor A is an intensityvalue which determines the proportion of change in voxel value withinthe Gaussian kernel. The factor A is not necessarily a static value andcan change throughout the iterations. If value of distance (d) isincreased from the baseline measurement (e.g., the distance between Pand Q based on the measured value and the original assigned value), thenthe perturbed voxel and surrounding region are adjusted down by an orderof magnitude using the above described Gaussian kernel transformation.If this value is decreased from the baseline measurement, then theperturbed voxel and surrounding region are adjusted up by an order ofmagnitude using the above described Gaussian kernel transformation.

The instructions 200 can further include repeating the iterative cycleuntil either a preset maximum number of iterations is reached or themeasurement error is less than a preset threshold, at 210. The presetmaximum is a maximum number of events until number the iterative cyclesare deemed to be sufficient. The preset maximum can be a number ofiterative cycles, an amount of time or other maximum attributes asdefined by the user. The preset threshold is a boundary set for themeasurement error. The preset threshold can be less than 5 percenterror, such as less than 1 percent error.

FIGS. 3A-3C depict a NIRS system 300 in operation according to anembodiment disclosed herein. The NIRS system 300 includes a NIRS device301 with a support 302 with a plurality of radiation sources 304 and aplurality of detectors 306. The radiation sources 304 and the detectors306 may be substantially the same as the radiation sources 104 and thedetectors 106, described with reference to FIGS. 1A and 1B. In FIG. 3A,the radiation sources 304 and the detectors 306 are embedded in thesupport 302. The NIRS device 301 is positioned in connection with atissue 320. The tissue 320 can include a plurality of layers, such as afirst layer 322, a second layer 324 and a third layer 326. The firstlayer 322 can be skin layer, the second layer 324 can be an adiposelayer and the third layer 326 can be a muscle layer. The first layer322, the second layer 324 and the third layer 326 may be composed of oneor more individual sub-layers (not shown). Further, though the firstlayer 322, the second layer 324 and the third layer 326 are depictedhere as discrete layers, the layers may not form a distinguishableboundary. Hemoglobin 328 may be interspersed in the first layer 322, thesecond layer 324 and the third layer 326. The hemoglobin 328 can befound in distinct vessels (e.g., arteries, veins, arterioles, venules,and capillary beds) which are interspersed in the first layer 322, thesecond layer 324 and the third layer 326.

In operation, the radiation sources 304 of the NIRS system 300 produce aNIR radiation 310 which is directed toward the tissue 320. The NIRradiation 310 penetrates the first layer 322, the second layer 324 andthe third layer 326. The tissue 320 causes a distortion in thedirectionality of the NIR radiation 310, based on the scatteringproperty of the tissue. The scattering property of the tissue, includingthe scattering coefficient, relates to the composition of the tissue320. Table values can be used to determine the scattering coefficient ofspecific tissue types which may form the layers of the tissue 320.Further, the scattering coefficient can be determined using othermeasuring techniques, including optical techniques. If the scatteringcoefficient is low, the radiation would simply travel through and notreflect, refract or otherwise change direction. Without back-scattering,the NIR radiation 310 would not be received by the detector 306. Thelayers of the tissue 320, such as skin and adipose tissue, are highscatterers of the NIR radiation 310. As such, part of the NIR radiation310 is redirected back toward the detector 306. The absorptioncoefficient is a measured parameter and is determined by the absorptionof the NIR radiation 310 by the tissue 320 as a function of the originalradiation intensity.

In FIG. 3B, depicts back-scattered radiation 312 returning from thetissue 320. The back-scattered radiation 312 is the NIR radiation 310 ofFIG. 3A, as reduced by passing through the tissue 320 and by specificwavelengths at the hemoglobin 328. The back-scattered radiation 312 willbe affected by a variety of factors before being received by thedetector 306, such as the radiation angle of incidence, tissue type,depth of travel, absorption and the like. The back-scattered radiation312 will include the wavelengths provided by the radiation source 304without a portion of the NIR radiation 310 which is absorbed by thehemoglobin 328. The portion of the NIR radiation 310 that is absorbed bythe hemoglobin 328 and other factors (such as water and less plentifulchromophores) in relation to the total input of the NIR radiation 310 isused to create the map. The pathway of the NIR radiation 310 and theback-scattered radiation 312, though depicted as linear for clarity, isnot necessarily linear. The NIR radiation 310 and the back-scatteredradiation 312 will be back-scattered by numerous components of thetissue 320.

In FIG. 3C, the plurality of mean radiation paths 330 between each ofthe radiation sources 304 and each of the detectors 306 are depicted.These mean radiation paths 330 are an estimate of the paths traveled bythe back-scattered radiation 312 in the tissue 320 between each of theradiation sources 304 and each of the detectors 306. The mean radiationpaths 330 are based on empirical data collected above, the substancetraveled through, the scattering coefficient, the absorptioncoefficient, simulations of the optical path based on laws of physicsand other parameters. As described above, the mean radiation paths 330incorporate the expected paths of the NIR radiation 310 and theback-scattered radiation 312. The mean radiation paths 330 have anarcuate shape which diverges from the radiation source 304 to reach amaximum width at the midpoint and then converges toward the detector306. The arcuate shape is also referred to as a banana or canoe-likeshape with ends located at the radiation sources 304 and the detectors306. The back-scattering described in FIG. 3B creates the width found atthe midpoint of each of the mean radiation paths 330.

The NIRS system 300 will be configured to calculate the oxygenationvalue of each volume element of the matrix (also known as a voxel) as aweighted sum of the measured oxygenation of all mean radiation path 330volumes that each voxel belongs to. The NIRS system 300 will also beconfigured to process the oxygenation matrix to generate and displaytopographic and fMRI-like tomographic views of the blood perfusionwithin the tissue 320. The absorbance at each of the mean radiationpaths 330 of each combination of radiation sources 304 and detectors 306are compared to one another. The absorbance for each of the meanradiation paths 330 is determined in relation to the wavelengthabsorbed. The absorbance from the overlapping mean radiation paths 330or derived information from the absorbance is then plotted on acoordinate plane to produce a map.

By determining the area of overlap for the known mean radiation path, aportion of the absorbance for each of the mean radiation paths can beattributed to that portion based on the area of the overlap withconsideration of the x, y and z planes. The overlap of the areas ofoverlap as mapped on the x, y and z planes provides the threedimensional information regarding oxygenation in the tissue. Increasedoverlap of areas of overlap gives more accurate boundaries for HHb andHbO₂, as the absorbances will be different between mean radiation paths330. For example, comparison of the overlap absorbance of areas ofoverlap for mean radiation paths 330 with a wavelength range including660 nm with the overlap absorbance of overlapping mean radiation paths330 with a wavelength range including 660 nm will provide information onthe quantity of HHb in both of the areas of overlap for the meanradiation paths 330. Cross comparison between separate wavelengths, suchas a comparison of the overlap absorbance of areas of overlap for meanradiation paths 330 with a wavelength range including 660 nm and theoverlap absorbance of areas of overlap for mean radiation paths 330 witha wavelength range including 880 nm, will produce data regarding thepositioning of hemoglobin in the two regions as well as the comparativeoxygenation in the region of overlap. The comparative absorption data isthen mapped in a 3D matrix, such as through the use of the MATLABsoftware, available from Mathworks, Inc. located in Natick, Mass. AMATLAB algorithm can be used to generate a 3D matrix. The 3D matrix caninclude all combination of radiation sources 304 and detectors 306 ofthe NIRS device 300, or a portion thereof.

FIG. 4 depicts an example of a slice 400 of the absorbance detectedusing an NIRS device, according to an embodiment disclosed herein. Theslice 400 is the mapped absorption on a grid 402 for each of the meanradiation paths produced by an NIRS device at a specific depth. Theslice 400 depicts a region 404. The region 404 depicts the boundaries ofthe detected region, without regard for the presence of HHb or HbO₂. Theregion 404 is determined by the known positioning of the mean radiationpaths based on the position of the detectors and the radiation sourcesfor a given tissue. In further embodiments, the region 404 can bedetermined based on a base line absorbance at one or more of thewavelengths received from the radiation sources. Within the region 404are deoxygenated areas 408 and oxygenated areas 406. The intensity ofthe color for the oxygenated areas 406 and deoxygenated areas 408reflects the level of absorption at a specific wavelength, which willindicate the respective quantities of HHb and HbO₂ in the areas. Thedefinition of the boundaries of the oxygenated areas 406 anddeoxygenated areas 408 will be dependent on the sample size.

In embodiments where more detectors are used, the clarity of boundariesthe oxygenated areas 406 and deoxygenated areas 408 will increase. Theoxygenated areas 406 and deoxygenated areas 408 can be further used todetermine the boundaries of tissue components, such as venules,arterioles and capillary beds. A three dimensional map can be shown inslices, such as slice 400, by allowing the user to change betweendepths.

FIG. 5 depicts a map 500 of the absorbance detected using an NIRSdevice, according to an embodiment disclosed herein. The map 500 is acomposite of a plurality of slices, as described above in FIG. 4. Theslices are positioned based on depth such that the map 500 provides anthree dimensional view. The map 500 includes a 3D grid 502 whichprovides a frame of reference for the detected absorbances. The region504 depicts the boundaries of the detected region, without regard forthe presence of HHb or HbO₂, and is determined based on one or more ofthe methods described with reference to FIG. 3. Within the region 504are both oxygenated regions 506 and deoxygenated regions 508. The grid504 allows for direct comparison based on depth of the specific region,as well as length and width.

FIGS. 6A and 6B depict a block diagram of a method 600 for determiningperfusion of a tissue according to an embodiment disclosed herein. Themethod 600 can include transplanting a tissue, as in element 602. Thetissue comprises both oxygenated and deoxygenated hemoglobin. Generally,the tissue is transplanted from a donor site and is positioned at alocation of excised tissue. During the reconstructive process, thetransplanted tissue is positioned in connection with the native tissue.Various preexisting arteries, arterioles, veins, venules and capillarybeds are reconnected between the native tissue and the tissuetransplanted from the donor region. This reconnection assures properperfusion of the transplanted tissue.

A first radiation source and a second radiation source are positioned inproximity to the tissue, as in element 604. The first radiation sourceand the second radiation source can be a radiation source as describedwith reference to FIG. 1A. The first radiation source and the secondradiation source are directed toward the tissue to deliver NIR radiationto the tissue. The first radiation source and the second radiationsource can have a fixed distance from one another. Further, the firstradiation source and the second radiation source can be positioned at afixed distance to one or more detectors. Though described here as tworadiation sources, a plurality of radiation sources may be used.

Once the radiation source is positioned, a first radiation can bedelivered to the tissue, as in element 606. The first radiation can havea wavelength range of between about 650 nm and about 1000 nm. The tissueis at least partially transparent to the first radiation allowing thefirst radiation to travel a distance in the tissue. As the tissue is nothomogenous, some components of the tissue, such as hemoglobin, willeither absorb the first radiation, transmit the first radiation orreflect the first radiation based on the wavelength of the firstradiation received. Radiation which is not absorbed is transmittedthrough the tissue creating a first transmitted radiation (also referredto as back-scattered radiation).

At least part of the first transmitted radiation is detected at a firstdetector, as in element 608. The first detector is positioned a firstdistance from the radiation source. The path that the radiation travelsfrom the radiation source to the detector is the mean radiation path.The first distance determines the length of the mean radiation path fromthe radiation source to the detector as well as the depth of thedetection. The hemoglobin, both HHb and HbO₂, within the mean radiationpath will provide information in the form of absorption of the firstradiation in the mean radiation path. The first transmitted radiationreceived at the detector can then be used in conjunction with otherinformation to determine the contents of the mean radiation path.

The wavelength used, as described above, is important to thedetermination of the contents of the mean radiation path. The firstdetector detects the intensity of the first transmitted radiation of thewavelength produced by the radiation source. The intensity of the firsttransmitted radiation delivered to the detector will be affected by theoverall amount of the first radiation within the mean radiation path andthe amount of the first radiation which is absorbed by components whichare spatially within the mean radiation path. The amount of the firstradiation within the mean radiation path is a function of the absorptioncoefficient and the scattering coefficient of each layer of the tissue,which is empirically determined either prior to or during themeasurement. The absorption is dependent on the wavelength used and theabsorbing components in the tissue, which in this case are HHb and HbO₂.Both subtypes absorb radiation of wavelengths between about 650 nm andabout 1000 nm to some degree. However, since 808 nm is the isosbesticpoint for HHb and HbO₂, the absorption by HHb is higher at wavelengthsbelow 808 nm and HbO₂ is higher at wavelengths above 808 nm.

Once the first transmitted radiation is detected, a second radiation canbe delivered from a second radiation source to the tissue, as in element610. The second radiation source can have a wavelength between about 650nm and about 1000 nm. The second radiation can be a single wavelength ora combination of wavelengths. Further, the second radiation can includeone or more of the same wavelengths as the wavelengths of the firstradiation. The tissue can absorb a portion of the second radiationcreating a second transmitted radiation.

The second transmitted radiation is then detected at the detectorpositioned a second distance from the second radiation source, as inelement 612. The path traveled by the second transmitted radiationthrough the tissue creates a second mean radiation path. The seconddistance may be the same as the first distance, such as when the firstradiation source and the second radiation source are positioned inconcentric circles which are at a specific radius from a centrallylocated detector.

The available radiation sources, such as the first radiation source andthe second radiation source, are multiplexed, assuring that any onedetector is only receiving radiation from one radiation source at anygiven time. As used herein, “multiplexed” refers to the delivery of theradiation from the source to the tissue and ultimately to each of thedetectors, such that each of the detectors only receive radiation fromone source at any given time. In one embodiment, multiplexing is done bytiming the radiation delivery of each radiation source, such that nomore than one radiation source is delivering radiation at any giventime. Here, the first radiation is emitted from the first radiationsource and a portion of the first radiation is received by the detectoras the first transmitted radiation. Once the first transmitted radiationis received, the second radiation source emits the second radiation, aportion of which is received by the same detector. Thus when using timemultiplexing, only one optical source is active at a time. Hence, thelight detected by one or more photodetectors can be associated with theonly radiation source active in that moment. Multiplexing the radiationsources both allows the control unit to differentiate between thesources of the radiation and allows for a larger number of meanradiation paths.

Though the multiplexing above is described with relation to time, theseparation of optical signals emitted by distinct emitters (i.e., indistinct locations and/or distinct wavelengths) towards one (or more)photodetectors can be achieved with several techniques, such as timemultiplexing (described above), frequency multiplexing, and codemultiplexing.

With frequency multiplexing, the radiation sources are separated basedon the frequency of the radiation produced by the radiation sources,such that the radiation sources can emit radiation simultaneously. Toseparate the signals received by the detector, the active radiationsources are modulated at a different frequency. In one example, threeradiation sources, R1, R2 and R3, deliver radiation at 660 nm to atissue. The wavelengths used herein are exemplary. Any wavelength orrange of wavelengths for the determination of HbO2 and HHb as describedh may be used. As described here, R1 produces the 660 nm radiation at afirst frequency, F1; R2 produces the 660 nm radiation at a secondfrequency, F2; and R3 produces the 660 nm radiation at a thirdfrequency, F3. As R1, R2 and R3 are delivering their radiationsimultaneously, the radiation will be received at the detector as asingle composite signal. The single composite signal yielded by thedetector can then be demodulated at frequencies F1, F2 and F3 toreconstruct the three radiation signals which would have been obtainedif the three radiation sources were emitted separately.

With code multiplexing, the radiation sources are separated based oninformation encoded into the radiation from the radiation sources, suchthat the radiation sources can emit radiation simultaneously. Toseparate the signals received by the detector, the active radiationsources are encoded with different codes. In one example, threeradiation sources, R1, R2 and R3, deliver radiation at 880 nm to atissue. As described here, R1 produces the 880 nm radiation with a firstcode, C1, embedded therein; R2 produces the 880 nm radiation with asecond code, C2, embedded therein; and R3 produces the 880 nm radiationwith a third code, C3, embedded therein. As R1, R2 and R3 are deliveringtheir radiation simultaneously, the radiation will be received at thedetector as a single composite signal. The single composite signalyielded by the detector can then be demodulated at frequencies F1, F2and F3 to reconstruct the three radiation signals which would have beenobtained if the three radiation sources were emitted separately. Thesingle composite signal yielded by the photodetector can then be decodedusing C1, C2 and C3 to reconstruct the three original signals whichwould have been obtained if the three sources were emitting in atime-multiplexed fashion.

Once the second transmitted radiation has been detected, an overlapabsorbance between the first mean radiation path and the second meanradiation path can be determined, as in element 614. The first meanradiation path is calculated to have a specific three dimensional shape,based on the tissue, the interdistance between the radiation source anddetector, scattering coefficient and other factors. The threedimensional shape of the mean radiation path is associated with thedetected absorbance for each of the first transmitted radiation (thefirst mean radiation path) and the second transmitted radiation (thesecond mean radiation path). Assuming that there is overlap between themean radiation path for the first transmitted radiation and the secondtransmitted radiation, the overlap absorbance is then determined. Theoverlap absorbance is a weighted absorbance of each of the first meanradiation path and the second mean radiation path based on therespective intensities and the size of the overlap. The firstabsorbance, the second absorbance and the overlap absorbance incoordinate space act as in conjunction to provide position and intensityof the oxygenation state of the hemoglobin in the tissue.

The steps of delivery of the first radiation, the detection of the firsttransmitted radiation, the delivery of the second radiation, thedetection of the second transmitted radiation and the determining of theoverlap absorbance are then repeated using a plurality of firstradiation sources and a plurality of second radiation sources to createa plurality of overlap absorbances, as in element 616. A more completeview of the oxygenation can be derived by increasing the number ofsources and detectors as well as widening the space over which thedetection occurs. Overlapping mean radiation paths using wavelengthsboth above and below the isosbestic point, allow for positioning andseparation of HHb and HbO₂.

Finally, the plurality of overlap absorbances is then mapped on acoordinate plane, as in element 618. The position of the overlapabsorbance is known in comparison to the device. As such, the overlapabsorbances are then plotted on an x, y and z axis with relation to theposition of the device, where the position of the device is an arbitraryposition in the coordinate plane. The position of the device can bemapped as well. The higher the number of overlapping mean radiationpaths and the higher the number of overlapping areas of overlap atvarious wavelengths, the better the resolution of the image produced.Further, the longer the interdistance between the radiation sources andthe detectors, the deeper the mean radiation path. The method above canbe performed in a continuous fashion, such that the map of the tissue isupdated in near real-time.

FIG. 7 is a block diagram of a method 700 of transplanting a tissue,according to one embodiment. Tissue transplantation involves therelocation of a tissue from one site to another. By creating apre-transfer and post-transfer volumetric map, possible blockages oranomalies can be detected early before tissue damage occurs. The method700 can include positioning a near infrared spectroscopy (NIRS) devicein connection with a tissue portion located on a donor location of afirst body, the NIRS device being positioned for a near infraredmeasurement, at 702; collecting a first NIRS measurement using the NIRSdevice, the first NIRS measurement providing information regarding bloodoxygenation or tissue perfusion, at 704; removing the tissue portionfrom the donor location of the first body, at 706; transplanting thetissue portion to a recipient location of the first body or a secondbody, at 708; collecting a second NIRS measurement, the second NIRSmeasurement providing information regarding blood oxygenation or tissueperfusion, at 710; and comparing the first NIRS measurement to thesecond NIRS measurement to determine a change in blood oxygenation ortissue perfusion, at 712. The method 700 can be performed sequentiallyas shown.

The method 700 begins by positioning a near infrared spectroscopy (NIRS)device in connection with a tissue portion located on a donor locationof a first body, the NIRS device being positioned for a near infraredmeasurement, at 702. The NIRS device can be a NIRS device as describedabove in FIG. 1A-1D. Further, the NIRS device may includemachine-readable instructions as described with relation to FIG. 2. Thetissue portion can be positioned directly in contact with the NIRSdevice or intervening structures may be used. The tissue type may be avariety of tissue types including combinations of tissue types, such asepithelial tissue or adipose tissue.

With the NIRS device in position, a first NIRS measurement is collectedusing the NIRS device, the first NIRS measurement providing volumetricinformation regarding blood oxygenation or tissue perfusion, at 704. Thefirst NIRS measurement can be a baseline measurement, which providesvolumetric information as to tissue perfusion, comparativeconcentrations of HHb or HbO₂ or other oxygenation parameters. Futuredata can then be compared to the first NIRS measurement. Further, thefirst NIRS measurement may be a combination of any oxygenationparameters, including any oxygenation parameters listed or describedherein. In another embodiment, the first NIRS measurement is compared toa baseline oxygenation parameter, such as to determine if the tissue iscapable of being used in a transplant. The first NIRS measurement is avolumetric measurement of the tissue, providing three dimensional dataregarding the oxygenation parameter or parameters.

After collecting the first NIRS measurement, the tissue portion can beremoved from the donor location of the first body, at 706. The tissueportion can be removed from the donor site using techniques well knownin the art for transplantation of a tissue. In one embodiment, the NIRSdevice is left in place during the transfer process. The tissue can be asingle tissue type or composed of multiple types.

Though the NIRS device is described with reference to a tissue flap,this should not be read as limiting of possible uses. The NIRS devicecan be used in a variety of situation not related to transfer of atissue flap. The NIRS device can be used to assess healthy tissueperfusion during exercise or at rest; other disease states such aperipheral vascular disease/diabetic vascular compromise/coronary arterydisease and congestive heart failure; and for transplants of all types,to include skin flap tissue and organ transplantation (e.g., renal,heart, liver and possibly lung)—some of which could be done from outsidethe body, while other embodiments might involve just using itintraoperatively (e.g., when the heart is being rewarmed after bypass),or possibly left inside the body as a permanent monitoring device (anadjunct to an implantable pacemaker or defibrillator).

The tissue portion can then be transplanted to a recipient location ofthe first body or a second body, at 708. The recipient location can belocated on either the donor or a separate recipient. The tissue istransplanted using techniques that are well known in the art.

A second NIRS measurement can then be collected, the second NIRSmeasurement providing volumetric information regarding blood oxygenationor tissue perfusion, at 710. The second NIRS measurement collected willat least include one of the oxygenation parameters determined in thefirst NIRS measurement. The oxygenation parameter will be related to aphysiological event in the tissue. In one example, a lower oxygenationcan be related to a vascular occlusion. Though described as separateevents, the first NIRS measurement and the second NIRS measurement maybe derived from the same event or measurement. In one embodiment, thefirst NIRS measurement and the second NIRS measurement are data setsselected from a continuous measurement.

The first NIRS measurement to the second NIRS measurement can becompared to determine a change in blood oxygenation or tissue perfusion,at 712. The first NIRS measurement is related to the tissue as perfusedat the donor location and prior to disconnection from the nativevasculature. The second NIRS measurement occurs after the reconnectionof the tissue at the donor site. Thus, the comparison of the first NIRSmeasurement to the second NIRS measurement will show areas ofdeoxygenation, blood pooling occlusion or other issues which may needeither pharmaceutical or surgical intervention.

Methods, systems and devices described herein disclose the use NIRS toprovide more complete view of oxygenation in a tissue duringreconstructive surgery or to track tissue perfusion in the setting of alimb crush injury that has resulted in compartment syndrome. Bydirecting NIRS radiation of a specific wavelength toward a tissue in amultiplexed fashion, the absorbance of a known region and a knownwavelength by the tissue can be determined. The detected absorbances arethen plotted into a grid. These absorbances directly correlate with thelocation of HHb and HbO2, thus providing a map of blood flow to thetissue in a near-instantaneous fashion while avoiding user error.

While the foregoing is directed to embodiments of the inventions, otherand further embodiments of the inventions may be devised withoutdeparting from the basic scope thereof.

The invention claimed is:
 1. A method for tissue imaging in a transplanted tissue, sequentially comprising: positioning a near infrared spectroscopy (NIRS) device in connection with a tissue portion located on a donor location of a first body, the NIRS device being positioned for a near infrared measurement; collecting a first NIRS measurement using the NIRS device, the first NIRS measurement providing information to create a pre-transfer volumetric map regarding blood oxygenation or tissue perfusion; creating the pre-transfer volumetric map regarding blood oxygenation or tissue perfusion from the first NIRS measurement; removing the tissue portion from the donor location of the first body; transplanting the tissue portion to a recipient location of the first body or a second body; collecting a second NIRS measurement, the second NIRS measurement providing information to create a post-transfer volumetric map regarding blood oxygenation or tissue perfusion; creating the post-transfer volumetric map regarding bloody oxygenation or tissue perfusion from the second NIRS measurement; and comparing the pre-transfer volumetric map to the post-transfer volumetric map to determine a change in blood oxygenation or tissue perfusion.
 2. The method of claim 1, wherein the NIRS device is connected with the tissue portion when the tissue portion is removed from the donor location and while the tissue portion is transplanted to the recipient location.
 3. The method of claim 1, wherein the NIRS device comprises a plurality of first radiation sources, a plurality of second radiation sources and a plurality of detectors connected to a support.
 4. The method of claim 3, wherein the first radiation sources and the second radiation sources are multiplexed.
 5. The method of claim 4, wherein the first radiation sources each deliver a first radiation, and wherein the first radiation is a radiation with a wavelength between 650 nm and 800 nm.
 6. The method of claim 4, wherein the second radiation sources each deliver a second radiation, wherein the second radiation is a radiation with a wavelength between 800 nm and 1000 nm.
 7. The method of claim 4, wherein the first NIRS measurement and the second NIRS measurement are selected samples from a continuous NIRS measurement.
 8. The method of claim 1 wherein: the pre-transfer volumetric map comprises dimensions corresponding to the tissue portion located on the donor location of the first body; and the post-transfer volumetric map comprises dimensions corresponding to the tissue portion located on the recipient location of the first body or the second body. 